Natural Flavonoids Targeting Deregulated Cell Cycle Progression in Cancer Cells

Singh, Rana P.; Agarwal, Rajesh

doi:10.2174/138945006776055004

Cited by 91 publications

(79 citation statements)

References 77 publications

(144 reference statements)

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“…28,30 The flavonoids also modulated the several proteins that involved in cancer promotion for instance protein kinases, epidermal growth factor receptors, platelet derived growth factor receptors, vascular endothelial growth factor receptors and cyclin-dependent kinases. 28,31 As shown in Figure 4, group A has the highest level of phenolics, while group Chas the lowest level. Group B showed medium phenolic content compared with other groups.…”

Section: Discussionmentioning

confidence: 95%

Correlation of Anticancer Effects of 12 Iranian Herbs on Human breast Adenocarcinoma cells with antioxidant Properties

et al. 2015

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Introduction: Many of Medicinal plants have been investigated for possible anticancer properties. The correlation cytotoxic effect of herbs with antioxidant activity is unclear, yet. The aim of the present study was to examine the antioxidant contents and anticancer effects of 12 Iranian medicinal plants on proliferation of breast cancer, MCF-7, and epithelial normal, MCf-10A, cells. Methods: Free radical scavenging and total antioxidant capacities of herbal waters assessed by DPPH and FRAP methods, respectively. Their total phenolic contents and cell viability determined by Folin-Ciocalteu and MTT assays, respectively. Results: Among the herbs, group A which contained relatively highest total phenolics content, antioxidant and free radical scavenging activities inhibited significantly greater growth of breast cancer cells in a dose-and time-dependent manner as compared to other groups. These medicinal plants were not cytotoxic components against normal cells. Conclusion: Therefore our results indicated that anti proliferative effects of 12 selected Iranian herbs

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Section: Discussionmentioning

confidence: 95%

Correlation of Anticancer Effects of 12 Iranian Herbs on Human breast Adenocarcinoma cells with antioxidant Properties

et al. 2015

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“…Several lines of evidence indicate that ROS may be involved in human carcinogenesis: (a) some growth factors such as epidermal growth factor (EGF), insulin, and angiopoietin-1 increase ROS production in the cells for regulating cell migration and proliferation (3)(4)(5)(6); (b) natural antioxidants can inhibit cancer cell proliferation and tumor growth (7)(8)(9)(10); (c) high levels of ROS are observed in some cancer cells, which may induce DNA damage leading to genomic instability and tumor initiation (11,12); and (d) ROS induce the activation of mitogen-activated protein (MAP) kinase, nuclear factor nB (NF-nB), and activator protein 1, which are known to be associated with cancer development (13)(14)(15). However, under certain conditions, ROS increase proapoptotic molecules such as p53 and p38 MAP kinase and induce cellular apoptosis (16,17).…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species Regulate Angiogenesis and Tumor Growth through Vascular Endothelial Growth Factor

Xia¹,

Qiao²,

Liu³

et al. 2007

Cancer Research

441

309

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Reactive oxygen species (ROS) are associated with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. However, the direct roles of endogenous ROS production still remain to be elucidated. In this study, we found that high levels of ROS were spontaneously produced by ovarian and prostate cancer cells. This elevated ROS production was inhibited by NADPH oxidase inhibitor diphenylene iodonium (DPI) and mitochondria electron chain inhibitor rotenone in the cells. To further analyze the source of ROS production, we found that ovarian cancer cells have much higher expression of NOX4 NADPH oxidase, and that specific inhibition of NADPH oxidase subunit p47production. To analyze the functional relevance of ROS production, we showed that ROS regulated hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) expression in ovarian cancer cells. Elevated levels of endogenous ROS were required for inducing angiogenesis and tumor growth. NOX4 knockdown in ovarian cancer cells decreased the levels of VEGF and HIF-1A and tumor angiogenesis. This study suggests a new mechanism of higher ROS production in ovarian cancer cells and provides strong evidence that endogenous ROS play an important role for cancer cells to induce angiogenesis and tumor growth. This information may be useful to understand the new mechanism of cancer cells in inducing tumorigenesis and to develop new therapeutic strategy by targeting ROS signaling in human cancer in the future. [Cancer Res 2007;67(22):10823-30]

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“…Recent studies have suggested that there is a relationship between higher kava consumption and lower incidence of cancer (Steiner 2000;Sarris and Kavanagh 2009). Flavonoids synthesized from chalcone precursors, isolated from plants, have antiproliferative activities with therapeutic potential, while the chalcone flavokawain from medicinal plants is as one of the best-selling medicinal foods in European and American markets (Lebot et al 1992;Go et al 2005;Singh and Agarwal 2006). Flavokawain A, B, and C, constitute approximately 0.46%, 0.015%, and 0.012% of kava extracts, respectively (Dharmaratne et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Flavokawain B induces apoptosis of human oral adenoid cystic cancer ACC-2 cells via up-regulation of Bim and down-regulation of Bcl-2 expression

Zhao

Chao

Wan

et al. 2011

Can. J. Physiol. Pharmacol.

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Novel effective drugs are still urgently needed in the prevention and treatment of oral adenoid cystic carcinoma (ACC). In this study, we have assessed the antitumor potential and molecular mechanisms of flavokawain B (FKB) as a kava chalcone on the ACC-2 cell line in vitro. The results demonstrated that FKB could significantly inhibit the cell proliferation of ACC-2 in a dose-dependent manner that was associated with induced apoptosis and cell cycle G2-M arrest, and the half maximal inhibitory concentration (IC50) of flavokawain-B treatment for 48 h was estimated to be 4.69 ± 0.43 µmol/L. Mechanistically, FKB could induce the release of cytochrome c from mitochondria into the cytosol, and activate the cleavage of caspase-3 and, eventually, the poly(ADP-ribose) polymerase (PARP), in a dose-dependent manner, leading to marked apoptotic effect of ACC-2 cells. The apoptotic action of FKB was associated with the increased expression of proapoptotic proteins: Bim, Bax, Bak and a decreased expression of antiapoptotic Bcl-2. Among them, Bim expression was significantly induced by FKB, and knockdown of Bim expression by short-hairpin RNAs attenuated the inhibitory effect induced by FKB on ACC-2 cells. These results suggest Bim may be one of the potential transcriptional targets, and suggests the potential usefulness of FKB for the prevention and treatment of ACC.Key words: flavokawain B (FKB), apoptosis, Bcl-2, Bim, ACC-2.Résumé : Il existe toujours un besoin urgent de nouveaux médicaments efficaces pour la prévention et le traitement du carcinome adénoïde kystique (CAK). Dans la présente étude, nous avons évalué le potentiel antitumoral et les mécanismes moléculaires du flavokawain B (FKB), une chalcone issue du kava, sur les cellules CAK-2 in vitro. Les résultats ont montré que FKB a pu inhiber considérablement la prolifération des cellules CAK-2 en fonction de la dose administrée, ce qui été associé à l'arrêt du cycle cellulaire en G2-M et à l'induction de l'apoptose, et que la valeur CI 50 après le traitement au flavokawain B pendant 48 heures a été de 4,69 ± 0,43 µmol/L. Du point de vue des mécanismes, FKB a pu induire la libération du cytochrome c des mitochondries dans le cytosol, et activer le clivage de la caspase-3 et de la poly(ADP-ribose) polymé-rase (PARP) de manière dose dépendante, ce qui a eu un effet apoptotique marqué sur les cellules CAK-2. L'action apoptotique de FKB a été associée à la surexpression des protéines pro-apoptotiques Bim, Bax, Bak et à la sous-expression de la Bcl-2 antiapoptotique. FKB a particulièrement augmenté l'expression de Bim, et l'inhibition de cette expression par les petits ARN en épingle à cheveux a atténué l'effet inhibiteur induit par FKB sur les cellules CAK-2. Ces résultats donnent à penser que Bim pourrait être une cible de transcription potentielle et que FKB pourrait être utile pour la prévention et le traitement du CAK.

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Natural Flavonoids Targeting Deregulated Cell Cycle Progression in Cancer Cells

Cited by 91 publications

References 77 publications

Correlation of Anticancer Effects of 12 Iranian Herbs on Human breast Adenocarcinoma cells with antioxidant Properties

Correlation of Anticancer Effects of 12 Iranian Herbs on Human breast Adenocarcinoma cells with antioxidant Properties

Reactive Oxygen Species Regulate Angiogenesis and Tumor Growth through Vascular Endothelial Growth Factor

Flavokawain B induces apoptosis of human oral adenoid cystic cancer ACC-2 cells via up-regulation of Bim and down-regulation of Bcl-2 expression

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